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首页> 外文学位 >A novel design of integrin alpha2beta1 targeting peptide probe for molecular imaging in prostate cancer.
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A novel design of integrin alpha2beta1 targeting peptide probe for molecular imaging in prostate cancer.

机译：用于前列腺癌分子成像的整合素α2beta1靶向肽探针的新型设计。

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摘要

Prostate cancer is one of the leading causes of cancer-related deaths in the United States and Europe. Despite the fact that prostate-specific antigen (PSA) screening has greatly increased the number of patients with early stage prostate cancer who can be cured by radical prostatectomy, about 40% of prostate cancers are first detected at an advanced stage and half of these are found to be extracapsular at pathologic staging. Therefore, development of an accurate noninvasive imaging technique to detect primary, recurrent and residual prostate cancer is critical for the effective management of this group of patients.;Accumulating experimental evidence indicates that integrins presented on various tumor types are differentially expressed during tumor transformation, progression, and metastasis. Development of integrin cell expression profiles of individual tumors may have further potential in identifying a cell surface signature for a specific tumor type and/or stage. Multiple lines of literature studies indicated that the upregulation or overexpression of alpha2beta1integrin may correlate with tumor progression in human prostate cancer. For example, the more aggressive PC-3 cell line has the highest expression of alpha2beta1 integrin compared with other less aggressive cell lines, such as CWR-22 (medium expression of alpha2beta1) and LNCap (low expression of alpha2beta1). Noninvasive imaging of this receptor with radiolabeled peptides that specifically target alpha2beta1 integrin could therefore be useful to decipher the invasive potential of prostate cancers.;High sensitivity positron emission tomography coupled with computed tomography for anatomical evaluation, PET/CT, has become a critical diagnostic imaging tool in the identification of a diverse group of malignancies. In this study, we use the knowledge of chemistry, radiochemistry, biochemistry, biology and molecular imaging to develop clinically translatable alpha2beta1 integrin targeting PET probes for prostate cancer imaging. A series of alpha2beta1 integrin targeting peptides were synthesized and their specificity was verified both in vitro and in vivo at the molecular level in preclinical prostate tumor models. The success of the proposed study may provide a better understanding of basic biological mechanisms of prostate cancer, help us more appropriately select patients considered for anti-integrin alpha2beta1 treatment, and allow the evaluation of disease course and therapeutic efficacy at the earliest stages of treatment.
机译：在美国和欧洲，前列腺癌是与癌症相关的死亡的主要原因之一。尽管前列腺特异性抗原（PSA）筛查已大大增加了可以通过根治性前列腺切除术治愈的早期前列腺癌患者的数量，但大约40％的前列腺癌首先在晚期被发现，其中一半是在病理分期发现是囊外的。因此，开发准确的无创成像技术以检测原发性，复发性和残留性前列腺癌对于有效治疗该组患者至关重要。;大量的实验证据表明，在各种肿瘤类型上呈递的整合素在肿瘤转化，进展过程中差异表达。和转移。单个肿瘤的整联蛋白细胞表达谱的发展在识别特定肿瘤类型和/或阶段的细胞表面特征方面可能具有进一步的潜力。多个文献研究表明，α2β1整合素的上调或过表达可能与人前列腺癌的肿瘤进展有关。例如，与其他侵袭性较低的细胞系，例如CWR-22（α2beta1的中等表达）和LNCap（α2beta1的低表达）相比，侵略性更高的PC-3细胞系具有最高的alpha2beta1整联蛋白表达。因此，用特异性靶向α2β1整联蛋白的放射性标记肽对该受体进行非侵入性成像可能对破译前列腺癌的潜在侵袭性有用。高灵敏度正电子发射断层显像结合计算机断层显像以进行解剖学评估，PET / CT已成为关键的诊断成像鉴定各种恶性肿瘤的工具。在这项研究中，我们利用化学，放射化学，生物化学，生物学和分子成像方面的知识来开发可针对前列腺癌成像的可临床翻译的alpha2beta1整合素靶向PET探针。合成了一系列α2beta1整合素靶向肽，并在临床前前列腺肿瘤模型的分子水平上在体内和体外验证了它们的特异性。拟议研究的成功可能会更好地了解前列腺癌的基本生物学机制，帮助我们更适当地选择考虑进行抗整合素α2β1治疗的患者，并允许在治疗的最早阶段评估疾病的病程和治疗效果。

著录项

  • 作者

    Huang, Chiun-Wei.;

  • 作者单位

    University of Southern California.;

  • 授予单位 University of Southern California.;
  • 学科 Health Sciences Radiology.;Health Sciences Oncology.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 182 p.
  • 总页数 182
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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